She broke into the comic book industry when still a teenager, scouted by Tom Long for his fanzine Graphic Showcase.[7] Long hired Doran to draw a revival of the 1940s character Miss Fury. Underage Doran quit the assignment due to its adult content.[4][8]

A Distant Soil was published in fanzines as early as 1979, then scouted by The Donning Company Starblaze imprint before it was contracted by WaRP Graphics. Doran left the company after nine issues due to an acrimonious dispute with WaRP,[9] which attempted to claim copyright and trademark on her work.[10][11][12] The WaRP version of the story has never been reprinted despite its unusual all-pencil style, and Doran's ownership of the publishing rights. She reprinted one short story in the Image Comics edition of the series that had appeared in a WaRP anthology.

After leaving WaRP, Doran discarded the 300 pages of published work, and rewrote and redrew the entire A Distant Soil story from scratch, first with Donning, then as a self-publisher: it is in multiple printings as a series of graphic novels, encompassing a single 1000 page long-form comics narrative, and has been published by Image Comics since 1996. It sold more than 700,000 copies.[13] The production archives were destroyed by the printer, and an extensive restoration process brought the book back to publication in April 2013, with a continuation of the comic series, and the first of its digitally restored print graphic novels and digital books appearing in July 2013.[14]

Doran is featured in the films Ringers (a documentary about The Lord of the Rings fans), Scenes From the Small Press: Colleen Doran by Rich Henn, Sex, Lies and Superheroes, the documentary The Cartoonist about Bone creator Jeff Smith,[17] and Captured Ghosts, a documentary about writer Warren Ellis.[18] She was also featured in the Dec. 12, 2011 episode of "Stalked: Someone's Watching," a Discovery ID television series that profiles stalking incidents, focusing on interviews with the actual victims.[19]

Gone to Amerikay a graphic novel drawn by Doran and written by Derek McCulloch was released in 2012 from DC/Vertigo. It is a "multi-generational Irish saga."[20] It was profiled in The Wall Street Journal,[21]Boing Boing[22] and Irish Echo.[23]Gone to Amerikay themed cover art was featured in the St Patrick's Day edition of Irish Echo, which was then presented to President Obama by Deputy First Minister Martin McGuinness of Northern Ireland. Gone to Amerikay was chosen for inclusion in the 2013 Best American Comics.[24]

Doran illustrated best-selling young adult novelist Barry Lyga's first graphic novel for Houghton Mifflin, Mangaman in 2011. It received a coveted starred review at Kirkus,[25][26] as well as awards at the New York Book Show and New England Book Builders of Boston, both granted to the design team.[27]

At the 2013 San Diego Comic Con, Matt Hawkins of Image Comics' Top Cow imprint announced Doran will illustrate his new comic series Control.[28] At the 2013 Image Comics Expo, it was announced that the series The Book of Lost Souls by J Michael Straczynski and illustrated by Doran will return to publication via the Image Comics imprint Joe's Comics.[29] She is also working with Neil Gaiman on an unnamed graphic novel for Dark Horse.[30][31] DC Comics chose her to write The Vampire Diaries comic book series based on the TV show.

Doran lectures widely in venues such as the Smithsonian Institution in Washington, DC, The Singapore Writers Festival, the Comics Masterclass in Sydney Australia, and at the Maryland Institute College of Art. Doran also worked as a creator rights activist, as lobbyist in Washington DC, and served on the advocacy committee of the Graphic Artists Guild.[32] She spoke at CREATE: Protecting Creativity from the Ground Up at the Newseum in Washington DC, with Congresswoman Marsha Blackburn, Rick Carnes President of the Songwriters Guild of America, musician Suzanne Vega, and other artists and technology policy specialists.[32]

The character Thessaly in Neil Gaiman's Sandman is based on Doran.[33]